1-Halo-3,7,7,11,11-PENTAMETHYLDI-AND TRI-ENES

ABSTRACT

Aliphatic quaternary alkyl compounds having unsaturation at C2,3, C-4,5, and/or C-8,9 and intermediates therefor useful as insect control agents, lubricants, plasticizers and odorants.

United States Patent [451 Sept. 19, 1972 Henrick et al.

[5 1-HALO-3,7,7,l 1,1 l-PENTAMETHYLDI- AND TRI-ENES [72] Inventors: Clive A. Henrick; John B. Siddall,

both of Palo Alto, Calif.

[73] Assignee: Zoecon Corporation, Palo Alto,

Calif.

[22] Filed: Oct. 14, 1970 [211 App]. No.: 80,764

[52] US. Cl. ..260/654 R, 260/247, 260/268 R,

N, 360/562 R, 260/583 R, 260/583.6,

[51] Int. Cl ..C07c 21/02 [58] Field of Search ..260/654 R [56] References Cited FOREIGN PATENTS OR APPLICATIONS 233,538 5/1964 Switzerland ..260/654 R Primary Examiner-Leon Zitver Assistant Examiner-Joseph A. Boska AttorneyDonald W. Erickson [57] ABSTRACT Aliphatic quaternary alkyl compounds having unsaturation at C-2,3, C-4,5, and/or C-8,9 and intermediates therefor useful as insect control agents, lubricants, plasticizers and odorants.

3 Claims, No Drawings 1-HALO-3,7,7,l l ,1 l-PENTAMETHYLDl-AND TRI- ENES This invention relates to novel unsaturated quatemary alkyl compounds, intermediates therefor, syntheses thereof and the control of insects.

The novel unsaturated quaternary alkyl compounds of the present invention and derivatives thereof are represented by the following formulas:

alkyl, cycloalkyl, aralkyl or aryl; and

each of R and R is hydrogen, alkyl, cycloalkyl, phenyl, alkoxyalkyl, hydroxyalkyl, lower alkenyl, or, when taken together with the nitrogen atom to which they are attached, pyrrolidino, morpholi-no, piperidino, piperazino or 4-lower alkylpiprazino.

The compounds of formula A, B and C are-useful for the control of insects. The utility of these compounds as insect control agents is. believed to be attributable to their juvenile hormone activity. They are preferably applied to the immature insect, namely during the embryo, larvae or pupae stage in view of their ability to inhibit metamorphosis and otherwise cause abnormal development. These compounds are effective control agents for Hemipteran insects, such as Lygaeidae, Miridae and Pyrrhocoridae; Lepidopteran insects, such as Pyralidae, Noctridae and Gelechiidae; Coleopteran, such as Tenebrionidae; and Dipteran. The compounds can be applied at low dosage levels of the order of 0.001 pg. to l5.0 ;4g. per insect. Suitable carrier substances include liquid or solid carriers, such as water, mineral or vegetable oils, talc, vermiculite, natural and synthetic resins andsilica. Treatment of insects in accordance with the present invention is accomplished by spraying, dusting or exposing the insects to the vapor of the compounds of formulas A, B and C. Generally, a concentration of less than percent of the active compound is employed. The formulations can include insectattractants, emulsifying agents or wetting agents assist in the application and effectiveness of the active ingredient. In the application of the compounds, there is generally employed a mixture of the C-2,3 trans and cis isomers, the C-2,3 trans isomer being the preferred embodiment for the control of insects.

In the description following andhereinafter, each of I R and R is defined as hereinabove and R" is alkyl,

cycloalkyl, aryl or aralkyl.

The compounds of the present invention are prepared according to the following outlined syntheses.

The novel triene esters (A') are prepared ,by the reaction of the aldehyde (IV) with the carbanion of the formula Vlllz' k no 0 cm R0 (VIII) The phosphonate anion (VIII) is generated by treatment of the corresponding phosphonate with base, such as alkali metal hydride or alkali metal alkoxide, e.g. sodium hydride or sodium methoxide, inorganic solvent inert to the reaction, such as a hydrocarbon, ether or dialkylsulfoxide solvent, e.g. benzene, toluene, dimethylformamide, tetrahydrofuran, and the like. The reaction is conducted at a temperature of from about 20C to room temperature or above. The reaction of the phosphonate anion with the aldehyde is generally conducted at temperature of about 0C to room temperature or above. The phosphonate can be prepared as described by Pattenden et al., J. Chem. Soc. (C), 1984 and i997 (1968). The esters (A) are converted 65 into the corresponding acid (A; R is hydrogen) by hydrolysis with base, such as potassium carbonate or sodium carbonate in organic solvent, such as methanol .or ethanol. Other esters of the present invention can be prepared by transesterificiation or conversion of the acid into the acid halide by treatment with thionyl chloride, oxalyl chloride, or the like, and then reacting the acid halide with the alcohol corresponding to the ester moiety desired.

In the preparation of the diene esters of formula B, an aldehyde of formula IV is hydrogenatedusing palladium on charcoal or other catalyst to yield the saturated aldehyde (V') which is reacted with a phosphonate anion of formula IX using the conditions described above or with an ylid of formula X to yield the unsaturated ketone (VI).

The unsaturated ketone (V1) is then reacted with a phosphonate anion (X1) to yield the diene ester (8) or by Wittig reaction using the ylid (XII).

( (XII) Conversion of VI into B using phosphonate anion can be done using the same conditions as for conversion of IV into A: Wittig reactions are generally done at higher temperatures, such as from room temperature to reflux. The ylids are prepared from the corresponding phosphonium bromide or chloride by treatment with a base, such as butyl lithium, alkali metal hydride, alkali metal hydroxide or alkali metal carbonate in an organic solvent, such as toluene, benzene, or tetrahydrofuran, or water or aqueous organic solvent depending upon the particular base.

In the preparation of the diene esters of formula C, an aldehyde of formula IV is reacted with a phosphonate anion (X1) or ylid (X) to obtain the di-unsaturated ketone (V) which is hydrogenated selectively using palladium in basic medium, lithium and liquid ammonia, or the like, to yield the corresponding 3,4- dihydro ketone (VII). Suitable hydrogenation procedures are described by Augustine, Catalytic Hydrogenation", M. Dekker, New York, pages 60-62 (1965 Augustine, Reaction", M. Dekker, New York, pages 104-105 (1968) and House, Modem Synthetic Reactions, W. A. Benjamin, Inc., New York, pages 61-66 (1965). The ketone (VII) is then converted into an ester of formula C by reaction with a phosphonate anion of formula X1 or an ylid of formula XII. The esters B and C' can be hydrolyzed using base to obtain acids of formulas B and C wherein R is hydrogen.

The aldehydes of formula ,IV are prepared according to the following outlined synthesis.

(EH3 '0 /CH3 R-CCHzC-CH=O CH3 OH;

(3H3 n; CH: R(|2OH-CHCH=C CH3 CH3 1! (II) The ketone (I), prepared by the alkylation of phorone using an organo-copper complex prepared from lower alkyl lithium or lower alkyl magnesium halide and cuprous iodide, is reduced using lithium aluminum hydride or sodium borohydride to yield the alcohol (II). See Anderson et al., J. Amer. Chem. Soc. 92, 735 (1970) and Siddall et al., J. Amer. Chem. Soc. 91, 1853 (1969).. The alcohol (II) is then reacted with a lower alkyl vinyl ether in the presence of mercuric acetate to yield the vinyl ether (III) which, upon heating under inert atmosphere at a temperature of about to about 220C, generally 180 to 210C, in a sealed vessel, yields the unsaturated aldehyde (IV).

The compounds of formulas IV, V, VI and VII, in addition to their utility as intermediates for the insect control agents of formulas A, B and C, are useful in chemical syntheses in general, such as the preparation of perfumery additives and as odorants for perfumery compositions. The polyene esters of formulas A, B and C are useful lubricants and plasticizers for polymers, such as hydrocarbon polymers and chlorinated hydrocarbon polymers.

The compounds, ketones, nitriles and amides of formulas A, B and C can be prepared by the reaction of a ketone of formula V, VI or VII with a compound of the formula:

in the presence of base. The aldehydes (R is hydrogen) can be prepared using the procedure of Nagata et al., Tetrahedron Letters, No. 41, 4359-4362 (1968) or by reduction of an ester of formula A, B or C to the corresponding C-l alcohol which is then oxidized using manganese dioxide to the aldehyde. The ketones (R is R 9* hydrogen) can be prepared from the esters A, B, C by hydrolysis of the ester to the free acid which is then treated with organo-lithium, the organo group corresponding to the ketone moiety desired. The amides can be prepared by the reaction of an acid chloride or bromide with an amine or by treating the ester A, B or C directly with an amine salt prepared by treating the selected amine with butyl lithium, or the like. The alcholls and ethers thereof (R is CI-I OR are prepared by reduction of the ester A, B; or C using lithium aluminum hydride to the C-1 alcohol which is then etherified in a conventional manner. The amines can be prepared by reduction of the amide or by converting a G1 alcohol to the G1 bromide or chloride as by treatment with phosphorus trichloride, or the like, and then reacting the C-1 bromide or chloride with the desired amine.

The term alkyl, as used herein, refers to a straight or branched chain saturated aliphatic hydrocarbon group having a chain length of one to eight carbon atoms. The term lower alkyl, as used herein, refers to a primary or secondary alkyl group having a chain length of one to six carbon atoms. The term cycloalkyl," as used herein, refers to a cycloalkyl group of four to eight carbon atoms. The term aralkyl, as used herein, refers to an aralkyl group of seven to 12 carbon atoms, such as benzyl, phenylethyl, methylbenzyl and naphthylmethyl. The term aryl, as used herein, refers to an aryl group of six to 12 carbon atoms, such as phenyl, methylphenyl, naphthyl, and the like. The term hydroxyalkyl,"d as used herein, refers to an alkyl group substituted with one hydroxy group. The term alkoxyalkyl, as used herein, refers to an alkyl group substituted with one alkoxy group. The term lower alkenyl, as used herein, refers to an ethylenically unsaturated aliphatic hydrocarbon of up to six carbon atoms.

The following examples are provided to illustrate the present invention. Temperature is' given in degrees Centigrade.

EXAMPLE 1 A. To a suspension of cuprous iodide (25 g.) in 500 ml. of dry ether at 0 is added 150 ml. of 1.6M methyl lithium in ether at a moderate rate with stirring under argon. After about 20 minutes at 0, 14 g. of phorone in 30 ml. of ether is added slowly and the mixture stirred for about 0.5 hour. The mixture is then poured into rapidly stirred aqueous ammonium chloride (about 1 liter), allowed to stand and the layers separated. The ether layer is washed with saturated sodium chloride, the water layer is extracted with ether and combined with the ether phase and dried over sodium sulfate and filtered. The filtrate is evaporated in vacuo to yield 2,6,6-trimethylhept-2-en -4-one.

B. 100 Grams of ketone of Part A dissolved in a mixture of 100 ml. of anhydrous ether and 100 ml. of hexane is added dropwise to a suspension of g. lithium aluminum hydride in 500 ml. anhydrous ether at 0. The mixture is stirred for 90 minutes at 0, quenched by dropwise addition of water and extracted with ether. The extract is washed with brine and dried. Evaporation of the solvent and distillation of the residue gives 2,6,6-trimethylhept-2-en-4-ol.

C. 67 Grams of alcohol of Part B and 12 g. mercuric acetate (freshly recrystallized from ethanol containing 1 percent acetic acid) are dissolved in 600 ml. of ethyl vinyl ether and refluxed for eight hours. Another 12 g. mercuric acetate is added and the solution further refluxed overnight. The solution is cooled to 0 and 200 ml. of saturated potassium carbonate is added. After one hour stirring, the organic layer is separated and washed with brine. After evaporation of the solvent, the vinylether (III; R is methyl) is heated in a bomb under nitrogen for one hour at l952l0. After cooling to room temperature, the reaction product is filtered in hexane through a short column of Woelm neutral alumina (activity III) and distilled to yield 3 ,3 ,7 ,7-tetramethyloct-4-e n- 1 -al.

D. The process of Part A is repeated using each of ethyllithium, n-propylithium, i-propylithium and butyllithium in place of methyllithium to yield 2,6,6- trimethyloct-2-en-4-one, 2,6,6-trimethylnon-2-en-4- one, 2,6,6,7-tetramethyloct-2-en-4-one and, 2,6,6-

trimethyldec-2-en-4-one, respectively, which are reduced according to the procedure of Part B to the corresponding C-4 alcohol of formula II. Each of the thus-obtained alcohols is reacted with ethyl vinyl ether using the procedure of Part C above to yield the corresponding vinyl ether of formula III (R is ethyl, npropyl, i-propyl and n-butyl, respectively). The vinyl ethers are heated using the procedure of Part C above to yield the corresponding aldehyde, that is, 3,3,7,7- tetramethylnon-4-en- 1 -al, 3 ,3 ,7,7-tetramethyldec-4- en- 1 -al, 3,3,7,7,8-pentamethylnon-4-en- 1 -al and 3,3,7,7-tetramethylundec-4-en-l-al, respectively. Similarly, using n-hexyl lithium in place of methyl lithium, there is obtained, as the final products, 3,3,7,7- tetramethyltridec-4-en-l-al, by the processes of this example.

EXAMPLE 2 Sodium methoxide (from 200 mg. sodium and 12 ml. methanol) is added dropwise to a stirred solution of 1.8 g. of trans diethyl 3-ethoxycarbonyl2-methylprop-2- enyl phosphonate (VIII; R R ethyl) and l g. of 3,3,7,7-tetramethyloct-4-en-l-al in 50 ml. of dimethylformamide under nitrogen. The reaction mixture is left for one hour at room temperature and then water is added followed by extraction with ether. The ethereal extracts are washed with brine, dried and evaporated to yield trans/cis methyl 3,7,7,l1,1 l-pentamethyldodeca- 2,4,8-trienoate. The isomeric mixture can be chromatographed on silica or distilled for purification. The isomeric mixture is predominantly trans at C-2,3.

The foregoing procedure is repeated using sodium ethoxide in place of sodium methoxide to yield trans/cis ethyl 3,7,7,l 1,1 l-pentamethyldodecar2,4,8- trienoate.

The procedure of this example is repeated using sodium ethoxide in place of sodium methoxide and using each of the aldehydes of Example 1 (Part D) in place of 3,3,7,7-tetramethyloct--en-l-al to yield trans/cis ethyl 3,7,7,l 1,1 l-pentamethyltrideca-2,4,8-trienoate, trans/cis ethyl 3,7,7,l 1,1 l-pentamethyltetradeca- 2,4,8-trienoate, trans/cis ethyl 3,7,7,1 1,1 l,l2-hexamethyltrideca-Z,4,8-trienoate, trans/cis ethyl 3,7,7,l 1,1 1-pentamethylpentadeca-2,4,8-trienoate and trans/cis ethyl 3,7,7,l l ,1 l-pentamethylhepta-deca- 2,4,8-trienoate, respectively. Similarly, the corresponding methyl esters are prepared from the aldehydes of Example 1 (D) using the process of this example, The trans/cis isomeric mixture of each of the foregoing compounds is separable into the individual isoemrs using gas-liquid chromatography or fractional distillatron.

EXAMPLE 3 To a mixture of 250 mg. of sodium hydride in 2 ml. of tetrahydrofuran, with ice-cooling, is added 1.6 g. of trans diethyl 3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate in 5 ml. of tetrahydrofuran. Temperature is allowed to rise to room temperature and after 30 minutes, 1 g. of 3,3,7,7-tetramethyloct-4-en-l-al is added. After about one hour at room temperature, the mixture is extracted with ether. The ethereal extracts are washed with brine, dried and evaporated to yield trans/cis ethyl 3 ,7,7,1 1,1 l-pentamethyldodeca-2,4,8- trienoate (about 1:1 mixture of C-2,3 trans and cis isomers).

EXAMPLE 4 EXAMPLE 5 A. One gram of 5 percent palladium-on-aarbon and g. of 3,3,7,7-tetramethyloct-4-en-l-al is stirred in 50 ml. of ethanol under excess hydrogen at 1 atmosphere pressure and at room temperature until the theoretical amound of hydrogen is absorbed (about 48 hours). Then, 2 ml. of dichloromethane is added and the mixture filtered. The filtrate is concentrated under reduced pressure to yield 3,3,7,7-tetramethyloctan-l-al.

By use of the foregoing procedure, each of the aldehydes of Example I (D) is hydrogenated to the corresponding 4,5-dihydro compound.

B. To 126 mg. of a 57 percent dispersion of sodium hydride in oil is added pentane. The pentane is removed and the sodium hydride washed several times with pentane. To the washed sodium hydride is added 582 mg. of diethyl acetylmethylphosphonate (IX; R is ethyl) in 5 ml. of tetrahydrofuran at l0 under argon. After several minutes, the solution is transferred to a solution of 500 mg. of 3,3,7,7-tetramethyloctan-l-al in about 4 ml. of dry tetrahydrofuran under argon over a period of about minutes at room temperature. After about 2 hours, water is added followed by addition of ether and the layers separated. The organic layer is washed with saturated sodium chloride, dried over sodium sulfate and evaporated under reduced pressure to yield 6,6, l0,10-tetramethylundec-3-en-2one.

Similarly, each of 3,3,7,7-tetramethylnonan-l-al, 3,3,7,7-tetramethyldecan-l-al, 3,3,7,7,8-pentamethylnonan-l-al, 3,3,7,7-tetramethylundecan-l-al and 3,3,7,7-tetramethyltridecan-l-al is converted into 6,6,l0,lO-tetramethyldodec-3-en-2-one, 6,6,10,10- tetramethyltridec-3-en-2-one, 6,6, 10, 10,1 l-pen tamethyl-dodec-3-en-2-one, 6,6,10,10-tetramethyltetradec-3-en-2-one and 6,6, l 0, IO-tetramethylhexadec-3-en-2-one, respectively.

By use of the process of this example, other 2- ketones of formula VI are prepared.

C. 32.3 Grams of sodium hydride (57percent in oil) is placed in a dry lzl, 3-neck flask (fitted with a nitrogen inlet) and washed three times 100 ml. each) with dry pentane under nitrogen), carefully decanting only the solvent each time, into a beaker of ethanol. 400 Milliliters dry tetrahydrofuran is then added, the mixture cooled to 0, and 156.0 g. of diethyl carbethoxymethyl-phosphonate (XI; R R" ethyl) is added under nitrogen. The solution is stirred for 0.5 hour after addition is complete, and then 123.5 g. of 6,6,10,10- tetramethylundec-3-en-2-one in 250 ml. dry tetrahydrofuran over 0.5 hour period at room temperature under nitrogen. The mixture is stirred overnight and then poured into saturated NaCl at 0 and extracted with ether (3 X 200 ml.), the organic layers dried (CaSO.,) and concentrated under reduced pressure to yield trans/cis ethyl 3,7,7,l l,l l-pentamethyldodeca-2,4-dienoate which can be separated into the individual C-2,3 trans and cis isomers using gas-liquid chromatography or fractional distillation.

The above process is repeated using each of the 2- ketones of Part B as the starting material to yield trans/cis ethyl 3,7,7,l1,1l-pentamethyltrideca-2,4- dienoate, trans/cis ethyl 3,7,7,l 1,1 l-pentamethyltetradeca-2,4-dienoate, trans/cis ethyl 3,7,7,l 1,1 1,12- hexamethyltrideca-Z,4-dienoate, trans/cis ethyl 3,7,7,l 1,1 l-pentamethylpentadeca-2,4-dienoate and trans/cis ethyl 3,7,7,l 1,1 1-pentamethylheptadeca-2,4- dienoate, respectively.

By using diethyl carbomethoxymethylphosphonate in the process of Part C, the corresponding 2,4-diene methyl esters are obtained. Similarly, by use of the processes of this example, other esters of formula B are obtained.

EXAMPLE 6 A. The process of Example 5 (B) is repeated with the exception of using 3,3,7,7-tetramethyloct-4-en-l-al in place of 3,3,7,7-tetramethyloctan-l-al to yield 6,6, l 0, l 0-tetramethylundeca-3,7-dien-2-one. Similarly, each of the mono-unsaturated aldehydes of Example 1 (D) are converted into the corresponding di-unsaturated 2-ketonesof formula V, i.e. 6,6,10,10- tetramethyldodeca-3,7-dien-2-one, 6,6,10, l0- tetramethyltrideca-3,7-dien-2-one, 6,6,10,10,1'l-pentamethyldodeca-3 ,7-dien-2-one, 6,6,10, l0- tetramethyltetradeca-3,7-dien-2-one and 6,6,10, 10- tetramethylhexadeca-3 ,7-dien-2-one, respectively.

B. Each of the di-unsaturated ketones of Part A is reduced using lithium in liquid ammonia to yield the corresponding 3,4-dihydro compound of formula VII, that is, 6,6, 10, l O-tetramethylundec-7-en 2-one, 6,6,10, lO-tetramethyldodec-7-en-2-one, 6,6,10,10- tetramethyltridec-7-en-2-one, 6,6, l0,10,l l-pentamethyldodec-7-en-2-one, 6,6,10,10-tetramethyltetrade c-7-en-2-one and 6,6,10,10-tetramethylhexadec-7-en-2-one, respectively.

C. The 2-ketones of Part B are used as the starting material in the process of Example 5 (C) to yield the corresponding diene esters of formula C, that is trans/cis ethyl 3,7,7,l l,l l-pentamethyldodeca-2,8- dienoate, trans/cis ethyl 3,7,7,l 1,1 l-pentamethyltrideca-2,8-dienoate, trans/cis ethyl 3,7,7,ll,ll-pentamethyltetradeca-Z,8-dienoate, trans/cis ethyl 3 ,7,7,1 1,1 l, l 2-hexamethyltrideca-2,S-dienoate, trans/cis ethyl 3,7,7,ll,1l-pentamethylpentadeca-2,8- dienoate and trans/cis ethyl 3,7,7,l l,l l-pentamethylheptadeca-2,8-dienoate, respectively. The individual C-2,3 trans and cis isomers can be separated by gasliquid chromatography or fractional distillation. The corresponding methyl esters are obtained using the diethyl phosphonate anion of formula XI wherein R" is methyl.

EXAMPLE 7 A mixture of l g. of trans/cis methyl 3,7,7,l 1,1 l-pentamethyldodeca-Z,4,8-trienoate, ml. of methanol, 0.2 g. of sodium carbonate and 6 m1. of water is stirred at about 30 for about 24 hours. The mixture is then diluted with water, neutralized and extracted with EXAMPLE 8 One gram of thionyl chloride is added with stirring at room temperature to 0.5 g. of trans/cis 3,7,7,1 1,11- pentamethyldodeca-2,4,8-trienoic acid and the mixture heated at about 50 for minutes. Excess thionyl chloride is removed by evaporation and then t-butyl alcohol (about 2 equivalents) is added and the mixture heated at about 50 for about 5 minutes. Excess t-butyl alcohol is removed by evaporation to yield t'rans/cis tbutyl 3,7,7,1 1 ,1 1-pentamethyldodeca-2,4,8-trienoate which'is purified by chromatography. T

Similarly, by using other alcohols, such as cyclohexyl alcohol, benzyl alcohol, phenol, n-pentanol, n-hexyl alcohol or i-propanol in the foregoing procedure, the corresponding esters are obtained.

EXAMPLE 9 To a solution of 0.5 g. of trans/cis 3,7,7,l1,l1-pentamethyldodeca-2,4,8-trienoic acid in ml. of benzene is added with stirring an equivalent amount of potassium bicarbonate. The mixture is stirred until the evolution of carbon dioxide ceases and evaporated to yield potassium 3,7,7,l1,l1-pentamethyl-9-oxododec-2-enoate.

Alternatively, acid salts can be prepared by titrating the acid with an organic solution or aqueous organic solution of the desired metal.

EXAMPLE 10 To 1.6 g. of sodium hydride (57 percent in oil dispersion) in a 500 ml., 3-neck flask, fitted with a nitrogen inlet, is added 25 to 50 ml. of dry hexane or pentane and the mixture swirled under nitrogen. The Nal-l is allowed to settle and the solvent carefully decanted into a beaker containing ethanol. This rinsing process is repeated twice and 100 ml. dry tetrahydrofuran is added via syringe or pipet. Mixture is cooled in an ice-bath and 9.0 g. triethyl phosphonacetate (dried over molecular sieves) is added via additional funnel over a 10 minute period. Stir an additional one-half hour. The solution of the above anion is transferred via syringe to a 125 ml. addition funnel (with pressure equalizing arm) and is added over about 1 hour to 6.73 g. of 6,6,l0,10-tetramethyldodec-7-en-2-one at room temperature with stirring. The homogenous solution is then stirred overnight (18-24 hours). The mixture is then poured into saturated sodium chloride at 0 and extracted with ether. The organic phase is dried and concentrated under reduced pressure to yield trans/cis ethyl 3 ,7,7,1 1 l 1-pentamethyltrideca-2,S-dienoate which can be purified by chromatography or distillation.

EXAMPLE 1 l 41 Grams of 3,3,7,7-tetramethyloct-4-en-l-al and 78.4 g. of recrystallized (ethyl acetate) triphenylphosphineacetylmethylene [Ramirez et al., J. Org. Chem. 22, 41 (1957)] are refluxed in one liter of dry toluene for 18 hours, under nitrogen. Most of the solvent is removed in vacuo, 500 ml. pentane is added and the mixture filtered. The flask and the triphenylphosphine oxide filter cake are washed several times with pentane. The filtrate is concentrated in vacuo to yield 6,6,10,10- tetramethylundeca-3,7-dien-2-one.

then.

By use of the foregoing Wittig reaction, other aldehydes of formula IV are converted into the corresponding di-unsaturated 2-ketones of formula V11.

EXAMPLE 12 One gram of triphenylphosphineacetylmethylene and 450 mg. of 3,3,7,7-tetramethylnon-4-en-l-al are dissolved in 10 ml. toluene and refluxed under nitrogen overnight. The toluene is distilled off and the formed triphenylphosphine oxide crystallized by addition of pentane. Filtration and evaporation of the pentane gives a residue, which is further purified by preparative thin-layer chromatography, with the plate eluted with 15 percent ethyl acetate-hexane. Removal of the UV active band gives 6,6,10,10-tetramethyldodeca-3,7- dien-2-one.

EXAMPLE 13 One gram of 6,6,10,10-tetramethylundeca-3,7-dien- 2-one in 10 ml. of 0.3N potassium hydroxidezethanol over mg. of 5 percent palladium-on-charcoal is hydrogenated at room temperature and atmospheric pressure, until the theoretical amount of hydrogen is taken up, to yield 6,6,l0,10-tetramethylundec-7-en-2- one which is worked up by. filtration followed by evaporation under reduced pressure.

EXAMPLE 14 The diene esters (B') can be prepared in one step from the saturated aldehydes (V') by reaction with the phosphonate anions (VIII) using the conditions described herein for conversion of aldehyde 1V to the esters A.

EXAMPLE 15 One gram of 3,7,7,1 1,11-pentamethyltrideca-2,4,8- trienoic acid in 30 ml. of benzene and one mol of sodium hydride is stirred about 2 hours and then a slight excess of oxalyl chloride is added at about 0 and stirred for 1 hour. The product is worked up by removal of solvent in vacuo and extraction with pentane to yield 3,7,7,1 1,1 1-pentamethyltrideca-2,4,8-trienoyl chloride.

EXAMPLE 16 To 1.2 g. of a 57 percent dispersion of sodium hydride in oil is added pentane. The pentane is removed and sodium hydride washed several times with pentane. To the washed sodium hydride is added 4.7 g. of diethyl acetylmethylphosphonate in 40 ml. of dry tetrahydrofuran at 10 under argon. After several minutes, the solution is transferred to a solution of 4.4 g. of 6,6,l0,10-tetramethyldodeca-3,7-dien-2-one in about 30 ml. of dry tetrahydrofuran under argon slowly at room temperature. After about 4 hours, water is added followed by addition of ether and the layers separated. The organic layer is washed with saturated sodium chloride, dried over sodium sulfate and evaporated to yield 4,8,8,12,IZ-pentamethyltetradeca- 3,5,9-trien-2-one.

By use of the foregoing procedure, the ketones of Column 1 are converted into the respective ketones of Column 11.

4,8,8, l2,12-pentamethyltetradeca-3,5-dien-2-one, 4,8,8, 12,1 Z-pentamethyltetradeca-3,9-dien2-one, 4,8,8,12,12-pentamethyltrideca-3 ,5 ,9,-trien-2-one, 4,8,8 l 2, 1 2pentamethyltrideca-3,9-dien-2-one, 4,8,8,12,12-pentamethyltrideca-3,S-dien-Z-one, 4,8,8,12,l2,13-hexamethyltetradeca-3 ,5-dien-2-one, 4,8,8,l2,l2,13-hexamethyltetradeca-3 ,9-dien-2-one.

EXAMPLE 17 To a stirred solution of 2.5 g. of 3,7,7,ll,ll-pentamethyltrideca-2,4,8-trienoic acid in 30 ml. of dry ether is added slowly, at 23 ml. of a one molar solution of ethyl lithium in ether. After about 3 hours at 20, the mixture is poured into iced 1N hydrochloric acid (100 ml.) with vigorous stirring. The ether layer is separated, combined with ethereal washings of the aqueous phase, washed with water, saturated potassium bicarbonate, and then saturated brine, dried over magnesium sulfate and concentrated under reduced pressure to yield 5,9,9,13,l3-pentamethylpentadeca- 4,6,10-trien-3-one which is purified by high vacuum distillation or chromatography.

By methyl lithium cyclopentyl lithium and phenyl lithium in the foregoing procedure, there is obtained 4,8,8, 1 2, l 2-pentamethyltetradeca-3,5,9-trien-2-one, cyclopentyl 2,6,6,10,l0-pentamethyldodeca-l,3,7-trienyl" ketone and phenyl 2,6,6,l0,10-pentamethyldodeca- 1 ,3,7-trienyl ketone, respectively.

Similarly, each of 3,7,7,ll,ll-pentamethyltridecw 2,4-dienoic acid, 3,7,7,1 1,1 l-pentamethyltrideca-2,8- dienoic acid and 3,7,7,l1,1l-pentamethyldodeca- 2,4,8-trienoic acid is reacted with ethyl lithium to yield 5,9,9,13,13-pentamethylpentadeca-4,6-dien-3-one,

5 ,9,9,13 l 3-pentamethylpentadeca-4,10-dien-3-one and 5,9,9, 1 3,1 3-pentamethyltetradeca-4,6,10-trien-3- one, respectively.

EXAMPLE 18 A solution of 2 g. of methyl 3,7,7,ll,ll-pentamethyltrideca-Z,4,8-trienoate in 20 ml. of dry ether is added with,stirring to 0.4 g. of lithium aluminum hydride covered with ether at 0. After about 1 hour, 2.5 ml. of acetic acid is added. The mixture is washed with ice water and the ether phase dried and evaporated to yield 3,7,7,11,1l-pentamethyltrideca- 2,4,8-trien-1-ol.

Each of the esters,

methyl 3,7,7,l l ,1 l-pentamethyltrideca-2,4-

dienoate,

methyl 3,7,7,l l ,1 1-pentamethyltrideca-2,8-

dienoate,

methyl 3,7,7,l 1 ,1 1-pentamethyldodeca-2,4-

dienoate,

l 2 methyl 3,7,7,l 1,1 1-pentamethyldodeca-2,8-dienoate and methyl 3,7,7,l 1,1 l-pentamethyldodeca-2,4 ,8-

trienoate 5 is reduced using the foregoing process to yield the C-1 alcohols listed in Column III.

3 ,7,7,1 1,1 l-pentamethyltrideca-2,4-dien- 1 -ol,

3,7,7,11,11-pentamethyltrideca-2,8-dien-l-ol, 3,7,7,l 1,1 1-pentamethyldodeca-2,4-dien-1-ol, 3 ,7,7,1 1,1 1-pentamethyldodeca-2,8-dien- 1 -ol, 3 ,7,7,1 1,1 1-pentamethyldodeca-2,4,8-trien-1-ol.

EXAMPLE 19 A mixture of 2 g. of 3,7,7,l 1,1 l-pentamethyltrideca- 2,4,8-trien-1-ol, 10 g. of manganese dioxide and 30 ml. of methylene dichloride is prepared by the slow addition of manganese dioxide so that the temperature does not exceed about 30. The mixture is then shaken for 4 hours, under nitrogen, at room temperature. The mixture is then filtered and the solid washed with ether. The filtrate and washings are combined and evaporated to yield 3,7,7,1 1,1 l-pentamethyltrideca-2,4,8-trien-lal which can be purified by distillation or chromatography.

By use of the foregoing process, the other allylic al- 30 cohols of Example 18 are oxidized to the corresponding C-l aldehydes.

EXAMPLE 20 To sodium hydride (0.7 g.), previously washed with hexane, under nitrogen, is added 75 m1. of dry tetrahydrofuran and then, after cooling to 0, 5.1 g. of diethyl phosphonoacetonitrile is added slowly. The mixture is stirred for about minutes and then added slowly to 6.8 g. of 6,6,10,l0-tetramethyldodeca-3,7- dien-2-one at room temperature with stirring. The mixture is stirred for about 12 hours and then poured into saturated sodium chloride at 0. The layers are separated and the organic layer dried over magnesium sulfate and evaporated to yield cis/trans 3,7,7,l1,l lpentamethyltrideca-2,4,8-trienenitrile.

The above process is repeated using each of the ketones of Column I as the starting material to'yield 3 ,7,7,1 1,1 l-pentamethyltrideca-2,4-dienenitrile,

3 ,7,7,1 1,1 l-pentamethyltrideca-2,8-dienenitrile,

3 ,7,7,1 1,1 1-pentamethyldodeca-2,4,8-trienenitri1e,

3 ,7,7,1 1,1 1-pentamethyldodeca-2,8-dienenitrile,

3,7,7, 1 1,1 1-pentamethyldodeca-2,4-dienenitrile, 3,7,7,l 1,1 1,12-hexamethyltrideca-2,4-dienenitrile and 3,7,7,1 1,1 1, l 2-hexamethyltrideca-2,8-dienenitrile.

EXAMPLE 21 LII Sodium hydride (1.7 g., 5 7 percent in oil) is washed,

three times with dry hexane. The hexane is removed and 15 ml. of dry tetrahydrofuran is added. N,N-diethyl diethoxyphosphonoacetamide (0.9 g.) dissolved in 5 ml. of dry tetrahydrofuran is added and stirred for about 40 minutes. Then 6,6,10,10-tetramethyldodeca- 3,7-dien-2-one in 5 ml. of dry tetrahydrofuran is added with stirring and cooling with an ice-bath. The ice-bath is removed after addition is completed and stirring continued for about 2 hours. Then the mixture is poured into water and extracted with ether. The ether extracts are combined, washed with water, dried over magnesium sulfate and evaporated under reduced pressure to yield cis/trans N,N-diethyl 3,7,7,11,11-pentamethyltrideca-2,4,8-trienamide.

The foregoing procedure is repeated using the ketones of Column I as the starting material to yield N,N-diethyl 3,7,7,l 1,1 l-pentamethyltrideca-2,4-dienamide, N,N-diethyl 3,7,7,1 1,1 1-pentamethyltrideca-2,8- dienamide, N,N-diethyl 3,7,7,1 1,1 l-pentamethyldodeca-2,4,8-trienamide, N,N-diethyl 3,7,7,l 1,1 l-pentamethyldodeca-2,8-dienamide, N,N-diethyl 3,7,7,1 1,1 l-pentamethyldodeca-2,4-dienamide, N,N- diethyl 3 ,7,7,1 1,1 l,l2-hexamethyltrideca-2,4-dienamide and N,N-diethyl 3,7,7,l1,11,12-hexamethyltrideca-2,8-dienamide.

By using other phosphonamides in the process of this example, such as N,N-dimethyl diethoxyphosphonacetamide, the corresponding amides are obtained, such as N,N-dimethyl 3,7,7,l l,l l-pen tamethyltrideca-2,4,8-trienamide.

EXAMPLE 22 Two grams of 3,7,7,l 1,1 1-pentamethyltrideca-2,4,8- trienoic acid chloride is added to 50 ml. of benzene, cooled to and saturated with ammonia under nitrogen. The mixture is allowed to stand for about one hour and then it is washed with water, dried over sodium sulfate and evaporated to yield 3,7,7,ll,ll-pentamethyltrideca-2,4,8-trienamide.

EXAMPLE 23 Three grams of 3,7,7,l 1,1 l-pentamethyltrideca- 2,4,8-trienoyl chloride in benzene is mixed with 2.5 g. of diethylamine in benzene and the resulting mixture allowed to stand at room temperature for about two hours. The mixture is concentrated under reduced pressure and the residue taken up in benzene, washed with dilute aqueous sodium bicarbonate and water, dried over sodium sulfate and evaporated to yield N,N- diethyl 3,7,7,1 1,1 l-pentamethyltrideca-2,4,8-trienamide.

By use of the foregoing procedure, each of dimethylamine, ethylamine, pyrrolidine, piperidine, aniline, morpholine and 2-methoxyethylamine is reacted with the acid chloride to yield the corresponding amide.

EXAMPLE 24 Two grams of 3,7,7,l1,ll-pentamethyltrideca-2,8- dienoyl chloride is added to a solution of 2 g. of 4-ethylpiperazine and 20 ml. of tetrahydrofuran. The mixture is allowed to stand for 4 hours at 0, then 50 ml. of benzene is added and the resulting mixture washed with water, drided over sodium sulfate and evaporated to yield N-(4'-ethylpiperazino) 3,7,7,l 1,1 l-pentamethyltrideca-2,8-dienamide.

EXAMPLE 25 To a mixture of 4 g. of 3,7,7,ll,ll-pentamethyltrideca-2,4,8-trien-l-ol and 25 ml. of benzene at 0 is added a solution of 5 ml. of phosphorus tribromide in 18 ml. of benzene over about minutes. The mixture is stirred at 0 for one hour and then heated at about 35 for two hours. The mixture is then poured onto ice and extracted with pentane. The organic phase is washed with aqueous sodium bicarbonate, water and then brine, dried over magnesium sulfate and evaporated to yield l-bromo-3,7,7,l 1,1 l-pentamethyltrideca-2,4,8-triene.

By use of the above process, the following bromides are prepared.

l-bromo-3 ,7,7,l 1,1 l-pentamethyltrideca-2,4-diene,

l-bromo-3,7,7,l 1,1 l-pentamethyltrideca-2,8-diene,

l-bromo-3,7,7,l 1,1 l-pentamethyldodeca-2,4-diene,

l-bromo-3,7,7,l 1,1 l-pentamethyldodeca-2,8-diene,

l-bromo-3,7,7,l 1,1 1-pentamethyldodeca-2,4,8-

triene.

By repeating the process of this example using phosphorus trichloride in place of phosphorus tribromide, the novel allylic chlorides are obtained.

EXAMPLE 26 Ten grams of l-bromo-3,7,7,1 1,1 l-pentamethyltrideca-2,4,8-triene is mixed with 50 ml. of benzene, cooled to 5l0 and saturated with ammonia. The resulting mixture is stirred for four hours allowing the temperature to rise to about 20 while maintaining dry conditions. The mixture is washed with dilute sodium hydroxide and the evaporated under reduced pressure to yield 3,7,7,l 1,1 1pentamethy1trideca-2,4,8- trienylamine.

Similarly, other allylic bromides are converted to the corresponding amine.

EXAMPLE 27 Five grams of l-bromo-3,7,7,l1,11-pentamethyltrideca-2,4,8-triene in 25 ml. of benzene is mixed with 4 g. of diethylamine and the mixture stirred for about 3 hours. Methylene chloride (50 ml.) is added and the mixture washed with dilute sodium hydroxide and then water and evaporated to yield N,N-diethyl 3,7,7,l 1,1 1- pentamethyltrideca-2,4,8-trienylamine.

The process of this example is repeated to prepare N,N-diethyl 3 ,7,7,1 1,1 l-pentamethyltrideca-2 ,4- dienylamine, N,N-diethyl 3,7,7,l 1,1 l-pentamethyltrideca-2,8-dienylamine, N,N-diethyl 3,7,7,l 1,1 l-pentamethyldodeca-Z,4-dienylamine, N,N-diethyl 3 ,7,7,1 1,1 l pentamethyldodeca-Z,8-dienylamine and N,N-diethyl 3,7,7,1 1,1 l-pentamethyldodeca-2,4 ,8- trienylamine from the allylic bromides of Example 25.

Similarly, by replacing diethylamine in the process of this example with other amines, such as dimethylamine, ethylamine, methylamine, pyrrolidine, morpholine, 4- ethylpiperazine, and the like, the corresponding amines of formulas A, B and C (R is CH NH R") are obtained.

EXAMPLE 28 To one g. of 3,7,7,l1,1l-pentamethyltrideca-2,4,8- trien-l-ol in 20 ml. of dry ether is added one molar equivalent of diazoethane. One drop of boron/trifluoride is added and the mixture allowed to stand 1 hour at 0 and then at room temperature for two additional hours. The mixture is then washed with water and organic phase evaporated to yield the ethyl ether of 3 ,7,7,1 1,1 1-pentamethyltrideca-2,4,8-tri-l-ol.

The use of diazomethane and diazopropane in the foregoing procedure affords the methyl ether and propyl ether.

Similarly, each of the allylic alcohols of Example 18 is converted into the corresponding ethyl ether, methyl ether and propyl ether.

EXAMPLE 29 One g. of 3,7,7,l1,1l-pentamethyltrideca-2,4,8- trien-l-ol in 10 ml. of diglyme is added dropwise to a slurry of 1 g. of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 g. of cyclohexylchloride. The reaction mixture is stirred at about 25 for 30 minutes and then quenched in ice water. The organic phase is separated and aqueous phase re-extracted with ether. The organic materials are washed with water, dried over sodium sulfate and evaporated to yield the cyclohexyl ether of 3,7,7,l 1,1 lpentamethyltridec a-2,4,8-trien- 1 -ol.

By using each of benzyl chloride, chlorobenzene, cyclopentyl chloride in the foregoing procedure, the corresponding benzyl ether, phenyl ether and cyclopentyl ether is obtained.

EXAMPLE 30 A mixture of 12 g. of l-bromo-3,7,7,l 1,1l-pentamethyldodeca-2,8-diene, 8 g. of thiourea and 5 ml. of water is stirred and heated under reflux for about 3 hours. A solution of 6 g. of sodium hydroxide in 60 ml. of water is added and the mixture refluxed with stirring for about 2 hours-The mixture is diluted with water and separated. The organic phase is washed with water and dried over magnesium sulfate to yield 3,7,7,l 1,1 1-

pentamethyldodeca-2,8-dieny1mercaptan which can be purified by chromatography.

By use of the above process, other C-l halides described herein are converted into the corresponding thiol.

EXAMPLE .31

To a solution of 2 g. of sodium in 50 ml. of methanol at 0 is added 4.5 g. of methylmercaptan. After about 0.5 hour, 20 g. of l-bromo-3,7,7,l1,11-pentamethyldodeca-2,8-diene is added and then the mixture refluxed for about 2 hours. The solvent is evaporated and the concentrate taken up in petroleum ether which is washed with water, dried over magnesium sulfate and evaporated under reduced pressure to yield methylmercaptan 3,7,7,l 1,1 l-pentamethyldodeca-2,S-dienyl (3,7,7,l 1 ,1 l-pentamethyldodeca-2,8-dienylthiomethane) which can be purified by chromatography.

EXAMPLE 32 To a solution of 2 g. of sodium hydroxide in 40 ml. of methanol saturated with hydrogen sulfide is added 10 g. of l-bromo- 3,7,7,l 1,1 l-pentamethyldodeca-Z ,4- diene. The mixture is stirred at about 24 for about 5 hours with continued introduction of hydrogen sulfide. The mixture is then diluted with water and extracted with petroleum ether. The organic phase is separated, washed well with water, dried over sodium sulfate and evaporated under reduced pressure to yield 3%?1l1 2fi trll832 fiifilfiffi which can be purified by chromatography.

By repeating the process of Example 31 using other mercaptans, such as ethylmercaptan, benzylmercaptan, phenylmercaptan and cyclopentylmercaptan, the corresponding thioethers and obtained.

What is claimed is:

l. A compound selected from those of the following formulas:

wherein X is bromo or chloro and R is lower alkyl. 2. A compound according to claim 1 wherein R is methyl or ethyl.

3. The compound, l-bromo-3,7,7,l 1,1 lpentamethyltri-deca-2,4,8-triene, according to claim 1. 

2. A compound according to claim 1 wherein R is methyl or ethyl.
 3. The compound, 1-bromo-3,7,7,11,11-pentamethyltri-deca-2,4,8-triene, according to claim
 1. 